Current issues in the epidemiology and toxicology of occupational exposure to lead.

Occupational exposure to lead is widespread in the United States. Clinically evident lead poisoning as well as subclinical toxicity occur in populations with occupational lead exposure. The focus of current research on lead toxicity in industrial populations is in the definition of dose-response relationships, particularly at low levels of exposure. Major interest surrounds the development of biochemical and physiologic markers of subclinical toxicity. Need exists to better delineate the toxicity of lead on the peripheral and central nervous system, the kidneys, the cardiovascular system, and the reproductive organs using newly developed markers. To obtain more accurate information on cumulative individual exposure to lead, future research on lead toxicity will increasingly use X-ray fluorescence analysis for determination of the lead content in home

Prevention of toxic environmental illness in the twenty-first century.

Previous introductions of new technologies have frequently resulted in unanticipated occupational and environmental illness. Prevention of such illness in the twenty-first century requires stringent application of two fundamental principles of public health: evaluation of new technologies before their introduction, and surveillance of exposed persons after the introduction of new technologies. Failure to establish these basic preventive mechanisms in advance will inevitably result in the development of new toxic diseases in the twenty-first century

Epidemiologic approaches to persons with exposures to waste chemicals.

Evaluation of disease in populations exposed to hazardous waste dumps requires: documentation of the chemicals in a dump; assessment of the materials released from the dump into environmental media; tracing of the probable routes of human exposure (groundwater, air, direct contact, or occupational); development, when possible, of individual exposure estimates and/or direct biological assessment of absorption; precise definition of the subpopulations at highest risk of exposure; and the employment of specific and sensitive health outcome indicators. Demonstration of dose-response relationships between chemical exposure and disease provides the most compelling evidence for a chemical etiology of illness in exposed populations. Interpretation of apparently negative data must be cautious, given the small size of most high-risk populations and the usual brevity of exposures

Strategies for epidemiologic studies of lead in bone in occupationally exposed populations.

Lead exposure is widespread among industrial populations in the United States. X-ray fluorescence (XRF) analysis of the lead content of bone offers a promising approach to acquisition of individualized data on chronic lead absorption in occupationally exposed populations. Dosimetric data obtained by XRF will permit accurate definition of dose-response relationships for such chronic consequences of lead exposure as central and peripheral neurologic impairment, renal disease. hypertension, and possibility reproductive dysfunction. Additionally, data on bone lead content obtained by XRF will permit validation of models describing the body lead burden and will allow direct assessment of the efficacy of therapeutic chelation. XRF data may also permit assessment of the possible role of genetic polymorphism of the enzyme delta-aminolevulinic dehydrase as a determinant of the pharmacokinetics and toxicity of lead. In both cross-sectional and prospective epidemiologic studies of body lead burden in occupationally exposed populations, the K-XRF instrument appears to be the technology of choice

The developing brain and the environment: an introduction.

mental retardation: timing and thresholds; (italic)b(/italic)) endocrine dysfunction and developmental disabilities: dose and target implications; (italic)c(/italic)) attention-deficit disorder-ADHD and learning disabilities; and (italic)d(/italic)) new horizons: extending the boundaries. Support for the Rochester conference came from both public and private sources. The National Institute of Environmental Health Sciences (NIEHS), the National Institute of Child Health and Human Development, and the EPA represented the federal government. The conference also received grants from several foundations: the Jennifer Altman Foundation, the Heinz Family Foundation, the National Alliance for Autism Research, the Violence Research Foundation, the Wacker Foundation, and the Winslow Foundation. The second of these conferences helped launch a new Center for Children's Health and the Environment at the Mount Sinai School of Medicine. It was held in New York City on 24-25 May 1999, and was convened specifically to consider the intersection between neurodevelopmental impairment, environmental chemicals, and prevention. Over 300 health scientists, pediatricians, and public health professionals examined the growing body of evidence linking environmental toxins to neurobehavioral disorders. The conference title was Environmental Influences on Children: Brain, Development, and Behavior. The conference began by reviewing well-known examples of deleterious effects of environmental chemicals, including lead and PCBs, on children's brains. The conferees then considered the potential impact of environmental chemicals on neurological disorders with particular focus on ADHD, autism, and Parkinson's disease. The inclusion of Parkinson's disease was intended to signal the notion that exposures in early life may have an influence on the evolution of neurological disease in later life. Support for the Mount Sinai conference came from the Superfund Basic Research Program (NIEHS); The Pew Charitable Trusts; the Institute for Health and the Environment at the University of Albany School of Public Health; the Agency for Toxic Substances and Disease Research (ATSDR); the Ambulatory Pediatric Association; Myron A. Mehlman, PhD; the National Center for Environmental Assessment (EPA); the National Center for Environmental Health (CDC); the National Institute of Child Health and Human Development; the Office of Children's Health Protection (EPA); Physicians for Social Responsibility; The New York Academy of Medicine; The New York Community Trust; and the Wallace Genetic Foundation. The impact of environmental toxins on children's health has become a topic of major concern in the federal government. Eight new research centers in children's environmental health have been established in the past 2 years with joint funding from EPA and NIEHS. Clinical units that specialize in the treatment of children with environmentally induced illness have been developed across the nation with grant support from ATSDR. The American Academy of Pediatrics has just published its (italic)Handbook of Pediatric Environmental Health (/italic)((italic)17(/italic)), the "Green Book," which is available to pediatricians throughout the Americas. Children's environmental health has climbed to a critical position as we launch the new millennium. This monograph marks a significant milestone in the evolution of this emerging discipline

Quantitative assessment of lives lost due to delay in the regulation of occupational exposure to benzene.

Benzene exposure can cause leukemia, aplastic anemia, and possibly lymphoma. In 1978, on the basis of strong but incomplete data then available on the risk of benzene-induced leukemia, the U.S. Occupational Safety and Health Administration (OSHA) reduced the permissible occupational exposure standard for benzene from 10 ppm to 1 ppm. Shortly thereafter, the Fifth Circuit Court of Appeals stayed this ruling, and in 1980, the Supreme Court overturned the regulation, citing insufficient evidence of benefit. Thus, from 1978 until the standard was again lowered to 1 ppm in 1987, American workers were exposed to benzene at levels in excess of 1 ppm. An estimated 9600 were exposed to levels between 1 and 10 ppm, and an additional 370 were exposed at levels above 10 ppm. To assess the risk resulting from this delay in regulation, we have conducted an epidemiologic risk analysis. We merged data on numbers of persons (238,000) exposed to benzene in seven occupational categories with dose-response data from three epidemiologic studies. The range of risk in these studies indicates that 44 to 152 excess leukemia deaths will ultimately result from exposure to benzene at 10 ppm over a working lifetime (45 years) and that lower or briefer exposures will result in proportionately fewer deaths. On this basis, we calculated that between 30 and 490 excess leukemia deaths will ultimately result from occupational exposures to benzene greater than 1 ppm that occurred between 1978 and 1987. Deaths from aplastic anemia and lymphoma will likely add to this toll. These data confirm the risk of regulatory delay. They suggest that the courts, in reviewing public health regulations, must beware of facile cost-benefit arguments and be willing to accept strong evidence of health risk even when such evidence is incomplete

Environmental neurotoxic illness: research for prevention.

Recognition of the deleterious neurological effects of chemicals has evolved from anecdotal observation to studies of illness in persons exposed to high doses. Now, the more subtle effects of exposures to environmental neurotoxicants are being documented: reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alteration of behavior. Substances to which millions of persons are exposed occupationally and in the general environment that can result in such deficits include lead, organophosphorus pesticides, certain chlorinated hydrocarbons, carbon disulfide, solvents, and mercury. The first step in the prevention of neurological impairments due to environmental exposures is to assess the toxicity of chemicals. Fewer than 10% of the 70,000 chemicals in commercial use have been evaluated for neurotoxicity. This knowledge gap needs to be narrowed by building on existing systems of toxicity testing. Concurrent with assessment of chemicals will be tiers of in vivo screening tests to measure functional and structural changes following exposures in vitro. Epidemiologic surveillance of populations at high risk will continue to inform on the ranking of suspect or known neurotoxicants. Research and researchers must become more sophisticated in the development and application of refined biologic markers so the findings can be used to detect absorption of toxicants and early neurological or neurobehavioral dysfunction before disability occurs and to protect human health and the environment